Traditionally, chelates have been used to administer poorly soluble salts in medicine and as antidotes for detoxification in cases of heavy metal or heavy metal isotope poisoning. Chelates have also been used to deliver radioisotopics to areas of the body for imaging and radiation therapy. Most recently, chelates with paramagnetic contrast agents have been reported for use as contrast agents in NMRI.
Paramagnetic metal ions are frequently toxic in the concentrations required for use in NMRI, and introducing them into the body in the form of chelates renders them more physiologically acceptable. This requires that a chelate be able to hold the metal ion tightly in the chelate structure, that is, the formation constant for the chelate must be very large at physiological pH. The paramagnetic metal chelate must also be sufficiently soluble to permit administration of quantities required for imaging in reasonably volumes of liquid. Usual routes of administration are oral, intravenous and by enema.
Since some paramagnetic metal ions may be released into the body, even from suitably stable chelates, paramagnetic metal ions which are naturally present in the body should be preferred. Manganese is naturally present in the body in trace quantities, and manganese(II) ions would be desirable paramagnetic materials if they could be formed into stable, soluble chelates. However, because manganese(II) is unstable in the presence of either reducing or oxidizing agents, the use of any chelating agent with an oxidizing or reducing group with manganese(II) was believed to be futile because redox reactions of the Mn(II)-chelate.
This invention provides a novel, highly stable manganese(II) chelate which meets the above objectives.